Mechanisms of metabolism other than those mediated by the mixed function oxidases may be important in activating certain chemicals to their ultimate carcinogenic form. Prostaglandin H synthetase is being used to activate compounds in mammalian cell mutation assays. Initial experiments showed hydrogen peroxide with sodium pyruvate. Using 5-phenyl-4-pentenyl hydroperoxide as a substrate, we have observed the mutagenic response to several chemicals. The possible mechanisms responsible for the formation of mutagenic metabolites induced by prostaglandin H synthetase as well as the mutation spectrum are being elucidated.